Will topical JAK inhibitors be launched?

Pharmas targeting atopic dermatitis target

HK inno.N enters a Phase 2 trial for atopic dermatitis treatment…the first among Korean pharmaceutical company

Incyte's Opzelura has been commercialized as the first atopic dermatitis treatment… Delgocitinib is waiting for FDA approval

Topical formulation of Janus kinase (JAK) inhibitors with the substantial advantage of administration convenience is entering the market for atopic dermatitis.

 

Unlike oral formulations, a topical drug formulation can be directly applied to the skin.

 

Thus, it has significantly improved treatment convenience.

 

To date, Incyte's Opzelura is the only JAK inhibitor approved by the U.S.

 

Food and Drug Administration (FDA).

 

Leo Pharma's delgocitinib is waiting for approval.

 

HK inno.N has entered the Phase 3 trial in South Korea.

 

HK inno.N is conducting a Phase 2 trial of topical JAK inhibitor…first in South Korea

According to industry sources on March 22, the Ministry of Food and Drug Safety (MFDS) has recently approved an Investigational New Drug (IND) application of the Phase 2 trial of HK inno.N's new drug candidate, 'IN-115314.' The clinical trial will evaluate the efficacy and safety of IN-115314 in adult patients with mild-to-moderate atopic dermatitis.

 

The trial's clinical research organization is the Korean University Ansan Hospital, and it will be investigated by Professor Sang Wook Son in the Department of Dermatology.

 

IN-115314 is a topical JAK inhibitor under development by HK inno.N.

 

This new drug candidate works by topically applied to the inflammatory areas and selectively inhibits JAK-1 kinase.

 

HK inno.N believes that IN-115314 has a lower amount of whole-body absorption than conventional drugs, thus presenting a low risk of side effects.

 

JAK inhibitors that are currently approved have various indications, including atopic dermatitis, ulcerative colitis, rheumatoid arthritis, and alopecia areata.

 

Considering the nature of externally applied drugs, companies focus on developing skin disorder products.

 

Notably, domestically approved JAK inhibitors, including AbbVie's Rinvoq, Lilly's Olumiant, Pfizer's Xeljanz, and Eisai's Jyseleca, have been developed exclusively as oral formulations.

 

Consequently, a topical formulation could offer significant advantages regarding dosing convenience.

 

In a Phase 1 clinical trial involving healthy adults, IN-115314 demonstrated favorable safety, tolerability, and pharmacokinetic profiles compared to the calcineurin inhibitor 'pimecrolimus' ointment, which is conventionally used in atopic dermatitis treatment.

 

HK inno.N plans to conduct a Phase 2 clinical trial as a correct-dose finding study in adult patients with atopic dermatitis.

 

Topical JAK inhibitor successfully commercialized…follow-up products are being actively developed Several topical JAK inhibitors overcome regulatory authority hurdles, so overseas companies are actively developing products.

 

Incyte

In 2021, the FDA approved U.S.-based Incyte's 'Opzelura' for the treatment of atopic dermatitis.

 

The active ingredient ruxolitinib in Opzelura cream was previously used under the product name Jakafi for treating cancer patients with conditions such as myelofibrosis, polycythemia vera, and chronic graft-versus-host disease.

 

Incyte successfully developed Opzelura as a treatment for atopic dermatitis based on Jakafi's JAK inhibitory mechanism.

 

Opzelura has been shown to alleviate inflammation and pruritus when applied topically in atopic dermatitis patients aged 12 and older.

 

In 2022, Insight secured U.S.

 

approval for Opzelura not only for atopic dermatitis but also for vitiligo.

 

Clinical development of Opzelura is ongoing, with Incyte currently conducting a Phase 3 trial in infants and children with atopic dermatitis.

 

The trial met its primary endpoints, including overall treatment success as assessed by the investigators.

 

Denmark's pharmaceutical company, LEO Pharma, has entered the competitive market by unveiling the latest clinical data for its topical JAK inhibitor delgositinib.

 

The company, specializing in dermatological drug development, successfully commercialized the biologic treatment 'Adtralza' for atopic dermatitis.

 

LEO Pharma

LEO Pharma is developing a topic formulation of delgositinib that targets JAK1, JAK2, JAK3, and TYK2.

 

TYK2 plays a critical role as a central link in the interleukin (IL)‑23 signaling pathway, which is pivotal in developing skin disorders such as psoriasis.

 

Last November, delgositinib received European marketing authorization under the brand name 'Anzupgo' for the treatment of chronic hand eczema (CHE), and it is currently awaiting FDA approval.

 

Delgositinib demonstrated exceptional improvement in clinical studies in patients with moderate-to-severe chronic hand eczema.

 

According to research presented at the American Academy of Dermatology earlier this month, in the clinical trials designated DELTA 1 and DELTA 2, 48% of patients achieved a deep response within 16 weeks, over 24% exhibited a consistent response, and 33% maintained their response even after discontinuing treatment.

 

Professor April Armstrong, affiliated with the David Geffen School of Medicine at UCLA, who presented the clinical results, said, "Delgositinib demonstrated approximately threefold higher efficacy than conventionally used treatments," adding, "Notably, the trial achieved significant advancement in difficult-to-treat patients with CHE."